The present invention is in the general area of polymeric device processing and in particular is a method of making bonded fiber structures of biocompatible polymers for use in cell culture and implantation.
The use of biodegradable polymers to regenerate metabolic organs, such as the liver and pancreas, and repair structural tissues like cartilage and bone by cell transplantation was recently reviewed by Cima, et al., "Hepatocyte Culture on Biodegradable Polymeric Substrates," Biotechn. Bioeng., 38, 145-158 (1991); Langer, et al., "Future Directions in Biomaterials," Biomaterials, 11, 738-745 (1990); Vatanti et al., "Selective Cell Transplantation Using Bioabsorbable Artificial Polymers as Matrices," J. Pediatr. Surg., 23, 3-9 (1988); and Vacanti, "Beyond Transplantation," Arch. Surg., 123, 545-549 (1988). To create organ function, donor material is obtained, the tissue is dissociated into individual cells, the cells are attached to a proper device, and the device is implanted to a place where the immobilized cells grow and function.
In addition to being adhesive substrates for cells, promoting cell growth, and allowing retention of differentiated cell function, materials used as templates for cell transplantation must be biocompatible and biodegradable, processable into desirable shapes, highly porous with large surface/volume ratios, and, finally, mechanically strong.
The polymer provides a sturdy scaffold to the transplanted cells and the means of organization to the ingrowing tissue. High porosity values are required in order to accommodate a large number of cells. As most cells are anchorage-dependent, large values of the total pore area are necessary for high cell growth rates. Also, the pore diameter or the interstitial distance must be much larger than the particular cell diameter and an interconnecting pore network structure is essential for tissue ingrowth, vascularization, and diffusion of nutrients, as reviewed by Vacanti, "Synthetic Polymers Seeded with Chondrocytes Provide a Template for New Cartilage Formation," Plast. Reconstr. Surg., 88, 753-759 (1991).
Poly(lactic-co-glycolic acid) (PLGA) fiber tassels and fiber-based felts fulfill many of the above material requirements and were initially utilized, as reported by Vacanti (1991) and Cima, et al., "Tissue Engineering by Cell Transplantation Using Degradable Polymer Substrates," J. Biomech. Eng., 113, 143-151 (1991), as transplantation devices for hepatocytes and chondrocytes to regenerate liver and cartilage function, respectively. In a recent paper, Freed, et al., "Neocartilage Formation In Vitro and In Vivo Using Cells Cultured on Synthetic Biodegradable Polymers," J. Biomed. Mater. Res., (in press), showed that chondrocytes cultured in vitro on poly(glycolic acid) (PGA) fiber meshes yielded after six weeks a cell density 8.3-fold higher than that at the first day and equaled the cellularity reported for normal bovine articular cartilage. However, although tassels and felts were useful in demonstrating the feasibility of organ regeneration, they sometimes lack the necessary structural stability. In order to be used for cell attachment and transplantation, they must often be configured into shapes similar to those of the repaired tissues, and also provide a firm substrate to the transplanted cells.
There remains a need for an improved method for making polymeric substrates for use in cell culture and implantation, which is efficient, economical and reproducible.
There is a further need for a method which yields polymeric matrices with the appropriate structure and porosity for use in maintaining cell viability and surfaces for attachment following implantation, even when cell masses and internal pressures on the implant increase.